tbuckley/cabot-search huggingface dataset:
Heterogeneity of generalized pustular psoriasis in multiethnic Johor Bahru, Malaysia
Authors: Tsen-Fang Tsai
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Heterogeneity of generalized pustular psoriasis in multiethnic Johor Bahru, Malaysia Get access Tsen-Fang Tsai Tsen-Fang Tsai Department of Dermatology, National Taiwan University Hospital, Taipei, Taiwan Correspondence: Tsen-Fang Tsai. Email: tftsai63@gmail.com https://orcid.org/0000-0002-1498-1474 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad197, https://doi.org/10.1093/bjd/ljad197 Published: 28 June 2023 Article history Received: 05 June 2023 Accepted: 06 June 2023 Published: 28 June 2023 Corrected and typeset: 05 August 2023
Injury Patterns and Hospital Admission After Trauma Among People Experiencing Homelessness
Authors: Casey M. Silver, Arielle C. Thomas, Susheel Reddy, Gwyneth A. Sullivan, Rebecca E. Plevin, Hemal K. Kanzaria, Anne M. Stey
Journal: JAMA Network Open (2023)

Importance Traumatic injury is a major cause of morbidity for people experiencing homelessness (PEH). However, injury patterns and subsequent hospitalization among PEH have not been studied on a national scale. Objective To evaluate whether differences in mechanisms of injury exist between PEH and housed trauma patients in North America and whether the lack of housing is associated with increased adjusted odds of hospital admission. Design, Setting, and Participants This was a retrospective observational cohort study of participants in the 2017 to 2018 American College of Surgeons’ Trauma Quality Improvement Program. Hospitals across the US and Canada were queried. Participants were patients aged 18 years or older presenting to an emergency department after injury. Data were analyzed from December 2021 to November 2022. Exposures PEH were identified using the Trauma Quality Improvement Program’s alternate home residence variable. Main Outcomes and Measures The primary outcome was hospital admission. Subgroup analysis was used to compared PEH with low-income housed patients (defined by Medicaid enrollment). Results A total of 1 738 992 patients (mean [SD] age, 53.6 [21.2] years; 712 120 [41.0%] female; 97 910 [5.9%] Hispanic, 227 638 [13.7%] non-Hispanic Black, and 1 157 950 [69.6%] non-Hispanic White) presented to 790 hospitals with trauma, including 12 266 PEH (0.7%) and 1 726 726 housed patients (99.3%). Compared with housed patients, PEH were younger (mean [SD] age, 45.2 [13.6] years vs 53.7 [21.3] years), more often male (10 343 patients [84.3%] vs 1 016 310 patients [58.9%]), and had higher rates of behavioral comorbidity (2884 patients [23.5%] vs 191 425 patients [11.1%]). PEH sustained different injury patterns, including higher proportions of injuries due to assault (4417 patients [36.0%] vs 165 666 patients [9.6%]), pedestrian-strike (1891 patients [15.4%] vs 55 533 patients [3.2%]), and head injury (8041 patients [65.6%] vs 851 823 patients [49.3%]), compared with housed patients. On multivariable analysis, PEH experienced increased adjusted odds of hospitalization (adjusted odds ratio [aOR], 1.33; 95% CI, 1.24-1.43) compared with housed patients. The association of lacking housing with hospital admission persisted on subgroup comparison of PEH with low-income housed patients (aOR, 1.10; 95% CI, 1.03-1.19). Conclusions and Relevance Injured PEH had significantly greater adjusted odds of hospital admission. These findings suggest that tailored programs for PEH are needed to prevent their injury patterns and facilitate safe discharge after injury.
VectorNet: collaborative mapping of arthropod disease vectors in Europe and surrounding areas since 2010
Authors: G.R. William Wint, Thomas Balenghien, Eduardo Berriatua, Marieta Braks, Cedric Marsboom, Jolyon Medlock, Francis Schaffner, Wim Van Bortel, Neil Alexander, Bulent Alten, Ewelina Czwienczek, Sofie Dhollander, Els Ducheyne, Celine M. Gossner, Kayleigh Hansford, Guy Hendrickx, Hector Honrubia, Tom Matheussen, Andrei Daniel Mihalca, Dusan Petric, Jane Richardson, Hein Sprong, Veerle Versteirt, Olivier Briet
Journal: Eurosurveillance (2023)

Background Arthropod vectors such as ticks, mosquitoes, sandflies and biting midges are of public and veterinary health significance because of the pathogens they can transmit. Understanding their distributions is a key means of assessing risk. VectorNet maps their distribution in the EU and surrounding areas. Aim We aim to describe the methodology underlying VectorNet maps, encourage standardisation and evaluate output. Method s: Vector distribution and surveillance activity data have been collected since 2010 from a combination of literature searches, field-survey data by entomologist volunteers via a network facilitated for each participating country and expert validation. Data were collated by VectorNet members and extensively validated during data entry and mapping processes. Results As of 2021, the VectorNet archive consisted of ca 475,000 records relating to &gt; 330 species. Maps for 42 species are routinely produced online at subnational administrative unit resolution. On VectorNet maps, there are relatively few areas where surveillance has been recorded but there are no distribution data. Comparison with other continental databases, namely the Global Biodiversity Information Facility and VectorBase show that VectorNet has 5–10 times as many records overall, although three species are better represented in the other databases. In addition, VectorNet maps show where species are absent. VectorNet’s impact as assessed by citations (ca 60 per year) and web statistics (58,000 views) is substantial and its maps are widely used as reference material by professionals and the public. Conclusion VectorNet maps are the pre-eminent source of rigorously validated arthropod vector maps for Europe and its surrounding areas.
<i>De Novo</i> and Histologically Transformed Small-Cell Lung Cancer Is Sensitive to Lurbinectedin Treatment Through the Modulation of EMT and NOTCH Signaling Pathways
Authors: Subhamoy Chakraborty, Charles Coleman, Parvathy Manoj, Deniz Demircioglu, Nisargbhai Shah, Elisa de Stanchina, Charles M. Rudin, Dan Hasson, Triparna Sen
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Small-cell lung cancer (SCLC) is a high-grade neuroendocrine tumor with dismal prognosis and limited treatment options. Lurbinectedin, conditionally approved as a second-line treatment for metastatic SCLC, drives clinical responses in about 35% of patients, and the overall survival (OS) of those who benefit from it remains very low (∼9.3 months). This finding highlights the need to develop improved mechanistic insight and predictive biomarkers of response. Experimental Design: We used human and patient-derived xenograft (PDX)-derived SCLC cell lines to evaluate the effect of lurbinectedin in vitro. We also demonstrate the antitumor effect of lurbinectedin in multiple de novo and transformed SCLC PDX models. Changes in gene and protein expression pre- and post-lurbinectedin treatment was assessed by RNA sequencing and Western blot analysis. Results: Lurbinectedin markedly reduced cell viability in the majority of SCLC models with the best response on POU2F3-driven SCLC cells. We further demonstrate that lurbinectedin, either as a single agent or in combination with osimertinib, causes an appreciable antitumor response in multiple models of EGFR-mutant lung adenocarcinoma with histologic transformation to SCLC. Transcriptomic analysis identified induction of apoptosis, repression of epithelial–mesenchymal transition, modulation of PI3K/AKT, NOTCH signaling associated with lurbinectedin response in de novo, and transformed SCLC models. Conclusions: Our study provides a mechanistic insight into lurbinectedin response in SCLC and the first demonstration that lurbinectedin is a potential therapeutic target after SCLC transformation.
Fecal microbiota transplantation in hematopoietic cell transplant and cellular therapy recipients: lessons learned and the path forward
Authors: Shaghayegh Habibi, Armin Rashidi
Journal: Gut Microbes (2023)

Disruptions to the gut microbiota have been associated with adverse outcomes including graft-versus-host disease, infections, and mortality after hematopoietic cell transplantation and cellular therapy. Evidence for causal links is accumulating, thus supporting therapeutic interventions targeting the microbiota with the goal of preventing and treating adverse outcomes. One such intervention is fecal microbiota transplantation (FMT) by which an entire community of gut microbiota is transferred to the patient with dysbiosis. As this approach in transplant and cellular therapy recipients is still in its infancy, no best approach has been defined and many open questions need to be addressed before FMT becomes a standard treatment. In this review, we highlight microbiota-outcome associations with the highest level of evidence, provide an overview of the main FMT trials, and suggest some paths forward.
Increase in invasive group A streptococcal infections and emergence of novel, rapidly expanding sub-lineage of the virulent Streptococcus pyogenes M1 clone, Denmark, 2023
Authors: Thor Bech Johannesen, Charlotte Munkstrup, Sofie Marie Edslev, Sharmin Baig, Stine Nielsen, Tjede Funk, Dennis Karsten Kristensen, Lars Hervig Jacobsen, Signe Fischer Ravn, Niels Bindslev, Sophie Gubbels, Marianne Voldstedlund, Pikka Jokelainen, Søren Hallstrøm, Astrid Rasmussen, Karl Gústaf Kristinsson, David Fuglsang-Damgaard, Ram B Dessau, Agnieszka Barbara Olsén, Christian Salgaard Jensen, Annette Skovby, Svend Ellermann-Eriksen, Thøger Gorm Jensen, Esad Dzajic, Claus Østergaard, Steen Lomborg Andersen, Steen Hoffmann, Peter Henrik Andersen, Marc Stegger
Journal: Eurosurveillance (2023)

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus .
Cyclin-Dependent Kinase 4/6 Inhibitors for Treatment of Hormone Receptor–Positive, ERBB2-Negative Breast Cancer
Authors: Ciara Catherine O’Sullivan, Robert Clarke, Matthew Philip Goetz, John Robertson
Journal: JAMA Oncology (2023)

Combination therapy with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i: palbociclib, ribociclib, abemaciclib) and endocrine therapy (ET) has been a major advance for the treatment of hormone receptor-positive (HR+), ERBB2 (formerly HER2)-negative (ERBB2-) advanced or metastatic breast cancer.
The PML hub: An emerging actor of leukemia therapies
Authors: Domitille Rérolle, Hugues de Thé
Journal: The Journal of Experimental Medicine (2023)

PML assembles into nuclear domains that have attracted considerable attention from cell and cancer biologists. Upon stress, PML nuclear bodies modulate sumoylation and other post-translational modifications, providing an integrated molecular framework for the multiple roles of PML in apoptosis, senescence, or metabolism. PML is both a sensor and an effector of oxidative stress. Emerging data has demonstrated its key role in promoting therapy response in several hematological malignancies. While these membrane-less nuclear hubs can enforce efficient cancer cell clearance, their downstream pathways deserve better characterization. PML NBs are druggable and their known modulators may have broader clinical utilities than initially thought.
US Cancer Mortality Trends Among Hispanic Populations From 1999 to 2020
Authors: Isabella R. Pompa, Anushka Ghosh, Shamik Bhat, Siri Ragala, Anita Nwiloh, Nabeel Rasheed, Fumiko Chino, Henning Willers, Saveli Goldberg, Sophia C. Kamran
Journal: JAMA Oncology (2023)

Advances in cancer research and treatment access have led to decreasing cancer mortality in the US; however, cancer remains the leading cause of death among Hispanic individuals.
Results of an Open-label, Phase Ia/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced, or Metastatic Soft-Tissue Sarcoma
Authors: Patrick Schöffski, Rastislav Bahleda, Andrew J. Wagner, Melissa A. Burgess, Niels Junker, Michael Chisamore, Patrick Peterson, Anna M. Szpurka, Matteo Ceccarelli, William D. Tap
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The study evaluated safety and efficacy of olaratumab + pembrolizumab in patients with unresectable locally advanced/metastatic soft-tissue sarcoma (STS) with disease progression on standard treatment. Patients and Methods: This was open-label, multicenter, nonrandomized, phase Ia/Ib dose-escalation study followed by cohort expansion (olaratumab + pembrolizumab intravenous infusion). Primary objectives were safety and tolerability. Results: The majority of patients enrolled (n = 41) were female [phase Ia: 9 of 13, phase Ib/dose-expansion cohort (DEC), 17 of 28], aged &amp;lt; 65 years. In phases Ia and Ib, 13 and 26 patients received prior systemic therapy, respectively. Patients received olaratumab 15 mg/kg (phase Ia; cohort 1) or 20 mg/kg (phase Ia; cohort 2 and phase Ib) and pembrolizumab 200 mg (phase Ia/Ib). The median (Q1–Q3) duration of therapy (olaratumab) was 6.0 (3.0–11.9; cohort 1), 14.4 (12.4–20.9; cohort 2), and 14.0 (6.0–21.8) weeks (DEC). No dose-limiting toxicities and few grade ≥ 3 treatment-emergent adverse events [TEAE; 15 mg/kg: 2 (increased lipase); 20 mg/kg: 1 (increased lipase), 1 (colitis), 2 (diarrhea), 3 (anemia)] were reported. Two TEAEs (increased lipase) were related to study discontinuations. Twenty-one patients reported mild (grade ≤ 2) TEAEs [phase Ia, disease control rate (DCR):14.3% (1/7, cohort 1); 66.7% (4/6, cohort 2); no responses were reported; phase Ib, DCR: 53.6% (15/28); objective response rate: 21.4% (6/28; RECIST and irRECIST criteria)]. No response was observed in patients with programmed death ligand-1–positive tumors. Conclusions: Antitumor activity was observed in some patients in DEC, and combination was well tolerated with manageable safety profile. Further studies are warranted to evaluate the efficacy and mechanistic impact of platelet-derived growth factor receptor inhibitors with immune checkpoint modulator coadministration.
Association Study Identified <scp><i>HLA‐DQA1</i></scp> as a Novel Genetic Risk of Systemic Lupus <scp>Erythematosus‐Associated</scp> Pulmonary Arterial Hypertension
Authors: Junyan Qian, Ying Chen, Xinzhuang Yang, Qian Wang, Jiuliang Zhao, Xiaoyue Deng, Yufang Ding, Shengjie Li, Yongtai Liu, Zhuang Tian, Juan Shen, Qijun Liao, Yanhong Wang, Xianbo Zuo, Xuejun Zhang, Mengtao Li, Yong Cui, Xueqing Yu, Xiaofeng Zeng
Journal: Arthritis & Rheumatology (2023)

Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE). However, the genetic signatures of SLE-associated PAH have not been well studied. We aimed to identify genetic variants implicated in SLE-associated PAH susceptibility within the major histocompatibility complex (MHC) region and assess the contribution to clinical outcomes.A total of 172 patients with SLE-associated PAH confirmed by right heart catheterization, 1,303 patients with SLE without PAH, and 9,906 healthy controls were included. Deep sequencing of the MHC region was performed to identify alleles, single-nucleotide polymorphisms, and amino acids. We compared patients with SLE-associated PAH with patients with SLE without PAH and healthy controls. Clinical association study was conducted to explore the contribution to phenotypes.A total of 19,881 genetic variants were identified within the MHC region. HLA-DQA1*03:02 was identified as a novel genetic variant associated with SLE-associated PAH in the discovery cohort (P = 5.68 × 10-12 ) and authenticated in an independent replication cohort (P = 1.30 × 10-9 ). The strongest associated amino acid position was mapped to HLA-DQα1 in the region affecting MHC/peptide-CD4+ T cell receptor affinity and antigen binding. Clinical association study demonstrated that patients with SLE-associated PAH with HLA-DQA1*03:02 had significantly lower rates of target role achievement (P = 0.005) and survival (P = 0.04).This study, based on the largest cohort of SLE-associated PAH, is the first to investigate how MHC region genetic variants contribute to SLE-associated PAH susceptibility. HLA-DQA1*03:02 is a novel genetic risk factor and a prognostic factor in SLE-associated PAH. Patients with SLE with this allele require regular monitoring and careful follow-up for early diagnosis and interventions for potential PAH.
Urinary Tract Infection, Bacteremia, and Meningitis Among Febrile Young Infants With SARS-CoV-2 and Non–SARS-CoV-2 Viral Infections
Authors: Brett Burstein, Alexandra Yannopoulos, Kelley-Anne Dionne
Journal: JAMA Network Open (2023)

This cohort study assesses the prevalence of urinary tract infections (UTIs), bacteremia, and bacterial meningitis among infants systematically tested for SARS-CoV-2 and non–SARS-CoV-2 viruses, with a focus on invasive bacterial infections.
Beliefs Among Veteran Firearm Owners Regarding Whether Clinicians Should Discuss Firearm Safety With Patients
Authors: Frances M. Aunon, Deborah Azrael, Joseph A. Simonetti, Matthew Miller
Journal: JAMA Network Open (2023)

Importance Veterans are at increased risk of suicide, and guidelines recommend assessing firearm access and counseling to reduce access among patients with elevated suicide risk. How veterans view such discussions is critical to the effectiveness of these interactions. Objective To assess whether veteran firearm owners believe clinicians should deliver firearm counseling when patients or their family members are being cared for in specific clinical contexts that suggest heightened risk of firearm injury. Design, Setting, and Participants In this cross-sectional study, data were from a probability-based online survey of self-identified veterans who reported owning at least 1 firearm (National Firearms Survey, July 1 to August 31, 2019) and were weighted to generate nationally representative estimates. Data were analyzed from June 2022 to March 2023. Main Outcomes and Measures Participants were asked, “As part of routine care, should physicians and/or other health care professionals talk with their patients about firearms and firearm safety if their patient or their patient’s family member (is at risk of suicide; has mental health or behavioral problems; is abusing or addicted to alcohol or drugs; is a victim of domestic violence; has Alzheimer’s disease or another dementia; or is going through a hard time).” Response options included “No,” “Yes, sometimes,” and “Yes, always.” In addition, responses were dichotomized as “Yes, at least sometimes” and “No.” Results Of 4030 adults who completed the survey (65% completion rate), 678 (mean [SD] age, 64.7 [13.1] years; 638 [92.9%] male) identified as veteran firearm owners. Across the 6 clinical contexts, support for clinicians “at least sometimes” discussing firearm safety as part of routine care ranged from 73.4% (95% CI, 69.1%-77.3%) when someone is “going through a hard time” to 88.2% (95% CI, 84.8%-90.9%) when someone has “mental health or behavioral problems.” When a patient or family member is at risk for suicide, 79.4% (95% CI, 75.5%-82.8%) of veteran firearm owners responded that clinicians should “at least sometimes” discuss firearms and firearm safety. Conclusions and Relevance This study’s findings suggest that most veteran firearm owners believe that clinicians should provide firearm counseling during routine care when a patient or family member is at heightened risk of firearm injury. These findings belie concerns that discussing firearm access with veteran firearm owners is an unacceptable practice.
The natural history of periodontal disease: The Java study—Origin, implementation, and results 35 years on
Authors: Ubele Van der Velden
Journal: Periodontology 2000 (2023)

Abstract This review describes the origin and results of the prospective longitudinal study to test potential prognostic indicators for periodontal breakdown in a population deprived of regular dental care. Experimental gingivitis studies in individuals highly susceptible or highly resistant to periodontitis showed that bleeding on probing developed quite differently: 50% versus 18% bleeding, respectively, after 18 days of no oral hygiene. This formed, together with other clinical and microbiological parameters, the basis for the 15‐year prospective study in the Java tea worker population to test potential prognostic indicators for periodontal breakdown. Evaluation showed that during the 15‐year observation period of this population aged 15‐25 years at baseline, the number of teeth decreased and the periodontal condition deteriorated. Gingival recession showed no increase during the first 7 years of observation, whereas a sixfold increase had occurred thereafter. Attachment loss doubled during the first 7 years, but almost tripled thereafter. Risk markers for disease onset/progression during the first 7 years of observation were age, the number of sites with subgingival calculus, and the subgingival presence of Aggregatibacter actinomycetemcomitans . Over the full period of 15 years the number of sites with a pocket depth of at least 5 mm and the number of sites with recession were identified as risk markers and male gender as a risk determinant. The prevalence of severe periodontitis amounted to 20% in 2002. Analysis showed that, already at baseline and throughout the study period, the periodontal condition in these individuals was more severe compared with the other participants. In conclusion, characteristics of susceptibility to periodontitis are already apparent in young adulthood.
JPH203, a LAT1 inhibitor, alleviates steroid‐resistant murine airway inflammation mediated by Th17 cells
Authors: Keitaro Hayashi, Mayumi Saeki, Kento Miura, Norimasa Yamasaki, Masaya Matsuda, Hayato Shimora, Takeshi Nabe, Yasuo Shimizu, Tomoe Fujita, Hitoshi Endou, Osamu Kaminuma
Journal: Allergy (2023)

Research data are not shared. Figure S1–S9. Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.